Human sperm mannose lectin has recently been established as a biochemical marker for the ability of sperm to bind to human eggs and undergo an acrosome reaction. Its expression on the sperm surface depends upon changes in plasma membrane composition. In this project we will study effects of selected heavy metals and oxidants upon expression of human sperm mannose lectin. This project is composed of three studies. [l) A prospective, case-controlled study of 90-125 workers with documented occupational exposures from metalworking . Semen and blood samples, taken pre-employment and after one year, will be assayed for toxicant levels, endocrine parameters and levels of species created by toxicant action upon cellular membranes. Fertility levels and effects of confounding variables will be assessed by questionnaire. Changes in will be compared to normal variability among 100 age frequency-matched, unexposed fertile males to determine significance. [2) An in vitro study of effects of the same toxicants upon sperm of 100 fertile males. Dose-response curves will be generated from duplicate aliquots of single samples. Levels of toxicant damage will be assessed to probe the molecular mechanisms of toxicant effects. Preliminary data from this study forms part of this application. [3] A survey of environmental exposure to these same toxicants, using 50- 100 normo-spermic infertile males, each also age frequency-matched to fertile male controls. Single blood and sperm samples will be taken from all subjects and the same parameters assayed. Results of these studies will include: [a] establishing blood and semen levels of metals and other toxicants associated with metalworking which can affect human sperm mannose lectin expression and reduce fecundity, [b] elucidating molecular mechanisms underlying actions of these toxicants on human sperm mannose lectin expression and upon human male fertility, [c] determining if normospermic infertile men with defects in mannose lectin expression, but no occupational exposure, differ from fertile men in levels of metal-associated toxicants in blood or semen, or if their sperm membrane compositions differ in a way to render them more liable to damage, and [d) demonstrating that mannose lectin expression assays are a quick, non-invasive means of assessing the hazard that potential toxicants present to human male fecundity, and of assessing the extent of damage after occupational or environmental exposure.